Prevalence and Overall Survival of Low Count Monoclonal B-Cell Lymphocytosis (LC-MBL): A Screening Study of 8,297 Individuals from the Mayo Clinic Biobank
Monoclonal B-cell lymphocytosis (MBL) is one of the most common pre-malignant conditions and is characterized by a circulating population of clonal B-cells with an absolute clonal B-cell count < 5x10 9/L and no evidence of lymphadenopathy, organomegaly, or cytopenias. MBL can be classified by the...
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| creator | Slager, Susan L. Parikh, Sameer A. Achenbach, Sara J. Kleinstern, Geffen Boddicker, Nicholas J. Norman, Aaron D. Rabe, Kari G. Lesnick, Connie E. Call, Timothy G. Olson, Janet E. Cerhan, James R. Kay, Neil E. Vachon, Celine M. Braggio, Esteban Hanson, Curtis A. Shanafelt, Tait |
| description | Monoclonal B-cell lymphocytosis (MBL) is one of the most common pre-malignant conditions and is characterized by a circulating population of clonal B-cells with an absolute clonal B-cell count < 5x10 9/L and no evidence of lymphadenopathy, organomegaly, or cytopenias. MBL can be classified by the immunophenotype: CLL-like MBL (CD5+, CD20dim), atypical MBL (CD5+, CD20+), or non-CLL-like MBL (CD5-, CD20+), as well as by the size of the clone (low-count or high-count) with low-count MBL (LC-MBL) defined as clonal B-cell |
| doi_str_mv | 10.1182/blood-2021-153320 |
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| fullrecord | <record><control><sourceid>elsevier_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1182_blood_2021_153320</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006497121045778</els_id><sourcerecordid>S0006497121045778</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1850-d4be441966bc6cb307d9255dc56596817595047c05c3db1bcbd49c80e9f37a003</originalsourceid><addsrcrecordid>eNp9kMtOwzAQRS0EEqXwAexmCRKGsRPnASsa8ZJSFamwjhLboYbURk4alF_ha0kpa1YjzdxzNTqEnDK8ZCzhV1XjnKIcOaNMBAHHPTJhgicUkeM-mSBiRMM0ZofkqG3fEVkYcDEh389e92WjrdRQWgWLXvuyaWC58b0ZD-BqyN0XZG5jO5g762Tj7Lif0UyPuXxYf66cHDrXmhbO8ozOZ_n5NdzCUnqtrbFvsOw2atgWJRc8jeHJKtMbtSmbFmrv1tCtNMzLwUHWGGskzIyrSvtxTA7qMaNP_uaUvN7fvWSPNF88PGW3OZUsEUhVWOkwZGkUVTKSVYCxSrkQSopIpFHCYpEKDGOJQgaqYpWsVJjKBHVaB3GJGEwJ2_VK79rW67r49GZd-qFgWGzlFr9yi63cYid3ZG52jB4f6432RSvNVqIyXsuuUM78Q_8AZWyBYQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Prevalence and Overall Survival of Low Count Monoclonal B-Cell Lymphocytosis (LC-MBL): A Screening Study of 8,297 Individuals from the Mayo Clinic Biobank</title><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Slager, Susan L. ; Parikh, Sameer A. ; Achenbach, Sara J. ; Kleinstern, Geffen ; Boddicker, Nicholas J. ; Norman, Aaron D. ; Rabe, Kari G. ; Lesnick, Connie E. ; Call, Timothy G. ; Olson, Janet E. ; Cerhan, James R. ; Kay, Neil E. ; Vachon, Celine M. ; Braggio, Esteban ; Hanson, Curtis A. ; Shanafelt, Tait</creator><creatorcontrib>Slager, Susan L. ; Parikh, Sameer A. ; Achenbach, Sara J. ; Kleinstern, Geffen ; Boddicker, Nicholas J. ; Norman, Aaron D. ; Rabe, Kari G. ; Lesnick, Connie E. ; Call, Timothy G. ; Olson, Janet E. ; Cerhan, James R. ; Kay, Neil E. ; Vachon, Celine M. ; Braggio, Esteban ; Hanson, Curtis A. ; Shanafelt, Tait</creatorcontrib><description><![CDATA[Monoclonal B-cell lymphocytosis (MBL) is one of the most common pre-malignant conditions and is characterized by a circulating population of clonal B-cells with an absolute clonal B-cell count < 5x10 9/L and no evidence of lymphadenopathy, organomegaly, or cytopenias. MBL can be classified by the immunophenotype: CLL-like MBL (CD5+, CD20dim), atypical MBL (CD5+, CD20+), or non-CLL-like MBL (CD5-, CD20+), as well as by the size of the clone (low-count or high-count) with low-count MBL (LC-MBL) defined as clonal B-cell <0.5x10 9/L or percent clonal B-cell count <85% out of total B-cell count. The prevalence of MBL varies depending on detection methods and population tested. In a Spanish screening study of 608 individuals, they identified 73 MBLs (12%) with CLL-like MBL; moreover, these authors also evaluated overall survival (OS) compared to 290 individuals without MBL and found a significantly shorter OS among these predominantly LC-MBLs. Here, we evaluate the prevalence and OS of LC-MBL in a large screening cohort of 8,297 individuals.
Study participants from the Mayo Clinic Biobank, a large-scale biorepository of adult patients, who had no prior history of hematologic malignancy, provided blood samples between 7/2009 to 4/2021. Stored peripheral blood mononuclear cells were screened for MBL with an eight-color flow cytometry assay capable of detecting clonal B-cell event to the 0.005% level. We classified each MBL by immunophenotype as CLL-like MBL, atypical MBL, and non-CLL-like MBL. Individuals with more than one immunophenotype were classified into one immunophenotype based on the following hierarchy: CLL-like MBL, then atypical MBL, then non-CLL like MBL. Based on previously published evidence, individuals were also classified by clonal counts using the percent clonal B-cell count <85% out of the total B-cell count to define LC-MBL. Individuals were followed from sample date to the earliest of death, loss to follow-up, or 5/31/2021. OS for LC-MBL and controls (individuals who screened negative for MBL) was assessed by Kaplan-Meier method. Age- and sex-adjusted OS was analyzed using inverse weights methods. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs), adjusted for age and sex.
We screened 8,297 individuals 40 years or older (median age 67 years, 39% male) and identified 1,326 (16%) with LC-MBL and 6,651 (80%) controls. Those individuals detected with high-count MBL (N=90, 1%) or individuals who had insufficient cells for flow cytometry interpretation (N=230, 3%) were excluded from subsequent analyses. The prevalence of LC-MBL was higher in males (21%) than females (14%; p<0.01) and significantly increased with age (p<0.01) ranging from 3% among those 40-49 years, 10% among those 50-59 years, 15% among those 60-69 years, 23% among those 70-79 years, and 29% for those 80+ years. Sixty-one individuals had clones with more than one type of immunophenotype. Based on our hierarchy, CLL-like MBL was the most common (N=1,155), followed by non-CLL-like (N=168) and atypical MBL (N=67). The median follow-up time in our cohort was 26 months (range 0-142), and 432 individuals had subsequently died. The 5-year and 10-year OS adjusted for age and sex among LC-MBLs was 95% and 87%, respectively; control estimates were 95% and 84%, respectively. We did not observe a significant difference in OS between those individuals with LC-MBL versus controls (HR=0.98, CI=0.77-1.24, P=0.84, Fig 1a), nor when we stratified individuals by age <65 (P=0.77) or age >= 65 (P=0.68). Among females, OS was longer among LC-MBL compared to controls (HR=0.61, CI=0.38-0.97, P=0.04); but no evidence of a difference in OS among males was observed (HR=1.22, CI=0.92-1.62, P=0.17). When we evaluated OS by MBL immunophenotype, we observed no statistically significant difference (Fig 1b, log rank P=0.44). When we stratified the MBLs by immunophenotype versus controls, we also did not observe a difference: CLL-like (HR=0.91, CI=0.71-1.18, P=0.5), atypical (HR=1.73, CI=0.92-3.27, P=0.09), non-CLL like (HR=0.98, CI=0.58-1.66, P=0.95).
In the largest MBL screening cohort to date, LC-MBL was a common condition among adults 40 years or older reaching a prevalence as high as 29% among individuals 80 years of age or older. OS among those with and without LC-MBL was similar, regardless of immunophenotype and age. The longer survival in females with MBL versus controls requires further evaluation.
[Display omitted]
Parikh: Pharmacyclics, AstraZeneca, Genentech, Gilead, GlaxoSmithKline, Verastem Oncology, and AbbVie: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics, MorphoSys, Janssen, AstraZeneca, TG Therapeutics, Bristol Myers Squibb, Merck, AbbVie, and Ascentage Pharma: Research Funding. Kay: Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding; Targeted Oncology: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Research Funding; Sunesis: Research Funding; Dava Oncology: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Behring: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Research Funding; MEI Pharma: Research Funding; Tolero Pharmaceuticals: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; CytomX Therapeutics: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios Pharm: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees. Shanafelt: Genentech, Pharmacyclics: Research Funding.]]></description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2021-153320</identifier><language>eng</language><publisher>Elsevier Inc</publisher><ispartof>Blood, 2021-11, Vol.138 (Supplement 1), p.2632-2632</ispartof><rights>2021 American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1850-d4be441966bc6cb307d9255dc56596817595047c05c3db1bcbd49c80e9f37a003</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Slager, Susan L.</creatorcontrib><creatorcontrib>Parikh, Sameer A.</creatorcontrib><creatorcontrib>Achenbach, Sara J.</creatorcontrib><creatorcontrib>Kleinstern, Geffen</creatorcontrib><creatorcontrib>Boddicker, Nicholas J.</creatorcontrib><creatorcontrib>Norman, Aaron D.</creatorcontrib><creatorcontrib>Rabe, Kari G.</creatorcontrib><creatorcontrib>Lesnick, Connie E.</creatorcontrib><creatorcontrib>Call, Timothy G.</creatorcontrib><creatorcontrib>Olson, Janet E.</creatorcontrib><creatorcontrib>Cerhan, James R.</creatorcontrib><creatorcontrib>Kay, Neil E.</creatorcontrib><creatorcontrib>Vachon, Celine M.</creatorcontrib><creatorcontrib>Braggio, Esteban</creatorcontrib><creatorcontrib>Hanson, Curtis A.</creatorcontrib><creatorcontrib>Shanafelt, Tait</creatorcontrib><title>Prevalence and Overall Survival of Low Count Monoclonal B-Cell Lymphocytosis (LC-MBL): A Screening Study of 8,297 Individuals from the Mayo Clinic Biobank</title><title>Blood</title><description><![CDATA[Monoclonal B-cell lymphocytosis (MBL) is one of the most common pre-malignant conditions and is characterized by a circulating population of clonal B-cells with an absolute clonal B-cell count < 5x10 9/L and no evidence of lymphadenopathy, organomegaly, or cytopenias. MBL can be classified by the immunophenotype: CLL-like MBL (CD5+, CD20dim), atypical MBL (CD5+, CD20+), or non-CLL-like MBL (CD5-, CD20+), as well as by the size of the clone (low-count or high-count) with low-count MBL (LC-MBL) defined as clonal B-cell <0.5x10 9/L or percent clonal B-cell count <85% out of total B-cell count. The prevalence of MBL varies depending on detection methods and population tested. In a Spanish screening study of 608 individuals, they identified 73 MBLs (12%) with CLL-like MBL; moreover, these authors also evaluated overall survival (OS) compared to 290 individuals without MBL and found a significantly shorter OS among these predominantly LC-MBLs. Here, we evaluate the prevalence and OS of LC-MBL in a large screening cohort of 8,297 individuals.
Study participants from the Mayo Clinic Biobank, a large-scale biorepository of adult patients, who had no prior history of hematologic malignancy, provided blood samples between 7/2009 to 4/2021. Stored peripheral blood mononuclear cells were screened for MBL with an eight-color flow cytometry assay capable of detecting clonal B-cell event to the 0.005% level. We classified each MBL by immunophenotype as CLL-like MBL, atypical MBL, and non-CLL-like MBL. Individuals with more than one immunophenotype were classified into one immunophenotype based on the following hierarchy: CLL-like MBL, then atypical MBL, then non-CLL like MBL. Based on previously published evidence, individuals were also classified by clonal counts using the percent clonal B-cell count <85% out of the total B-cell count to define LC-MBL. Individuals were followed from sample date to the earliest of death, loss to follow-up, or 5/31/2021. OS for LC-MBL and controls (individuals who screened negative for MBL) was assessed by Kaplan-Meier method. Age- and sex-adjusted OS was analyzed using inverse weights methods. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs), adjusted for age and sex.
We screened 8,297 individuals 40 years or older (median age 67 years, 39% male) and identified 1,326 (16%) with LC-MBL and 6,651 (80%) controls. Those individuals detected with high-count MBL (N=90, 1%) or individuals who had insufficient cells for flow cytometry interpretation (N=230, 3%) were excluded from subsequent analyses. The prevalence of LC-MBL was higher in males (21%) than females (14%; p<0.01) and significantly increased with age (p<0.01) ranging from 3% among those 40-49 years, 10% among those 50-59 years, 15% among those 60-69 years, 23% among those 70-79 years, and 29% for those 80+ years. Sixty-one individuals had clones with more than one type of immunophenotype. Based on our hierarchy, CLL-like MBL was the most common (N=1,155), followed by non-CLL-like (N=168) and atypical MBL (N=67). The median follow-up time in our cohort was 26 months (range 0-142), and 432 individuals had subsequently died. The 5-year and 10-year OS adjusted for age and sex among LC-MBLs was 95% and 87%, respectively; control estimates were 95% and 84%, respectively. We did not observe a significant difference in OS between those individuals with LC-MBL versus controls (HR=0.98, CI=0.77-1.24, P=0.84, Fig 1a), nor when we stratified individuals by age <65 (P=0.77) or age >= 65 (P=0.68). Among females, OS was longer among LC-MBL compared to controls (HR=0.61, CI=0.38-0.97, P=0.04); but no evidence of a difference in OS among males was observed (HR=1.22, CI=0.92-1.62, P=0.17). When we evaluated OS by MBL immunophenotype, we observed no statistically significant difference (Fig 1b, log rank P=0.44). When we stratified the MBLs by immunophenotype versus controls, we also did not observe a difference: CLL-like (HR=0.91, CI=0.71-1.18, P=0.5), atypical (HR=1.73, CI=0.92-3.27, P=0.09), non-CLL like (HR=0.98, CI=0.58-1.66, P=0.95).
In the largest MBL screening cohort to date, LC-MBL was a common condition among adults 40 years or older reaching a prevalence as high as 29% among individuals 80 years of age or older. OS among those with and without LC-MBL was similar, regardless of immunophenotype and age. The longer survival in females with MBL versus controls requires further evaluation.
[Display omitted]
Parikh: Pharmacyclics, AstraZeneca, Genentech, Gilead, GlaxoSmithKline, Verastem Oncology, and AbbVie: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics, MorphoSys, Janssen, AstraZeneca, TG Therapeutics, Bristol Myers Squibb, Merck, AbbVie, and Ascentage Pharma: Research Funding. Kay: Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding; Targeted Oncology: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Research Funding; Sunesis: Research Funding; Dava Oncology: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Behring: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Research Funding; MEI Pharma: Research Funding; Tolero Pharmaceuticals: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; CytomX Therapeutics: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios Pharm: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees. Shanafelt: Genentech, Pharmacyclics: Research Funding.]]></description><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kMtOwzAQRS0EEqXwAexmCRKGsRPnASsa8ZJSFamwjhLboYbURk4alF_ha0kpa1YjzdxzNTqEnDK8ZCzhV1XjnKIcOaNMBAHHPTJhgicUkeM-mSBiRMM0ZofkqG3fEVkYcDEh389e92WjrdRQWgWLXvuyaWC58b0ZD-BqyN0XZG5jO5g762Tj7Lif0UyPuXxYf66cHDrXmhbO8ozOZ_n5NdzCUnqtrbFvsOw2atgWJRc8jeHJKtMbtSmbFmrv1tCtNMzLwUHWGGskzIyrSvtxTA7qMaNP_uaUvN7fvWSPNF88PGW3OZUsEUhVWOkwZGkUVTKSVYCxSrkQSopIpFHCYpEKDGOJQgaqYpWsVJjKBHVaB3GJGEwJ2_VK79rW67r49GZd-qFgWGzlFr9yi63cYid3ZG52jB4f6432RSvNVqIyXsuuUM78Q_8AZWyBYQ</recordid><startdate>20211123</startdate><enddate>20211123</enddate><creator>Slager, Susan L.</creator><creator>Parikh, Sameer A.</creator><creator>Achenbach, Sara J.</creator><creator>Kleinstern, Geffen</creator><creator>Boddicker, Nicholas J.</creator><creator>Norman, Aaron D.</creator><creator>Rabe, Kari G.</creator><creator>Lesnick, Connie E.</creator><creator>Call, Timothy G.</creator><creator>Olson, Janet E.</creator><creator>Cerhan, James R.</creator><creator>Kay, Neil E.</creator><creator>Vachon, Celine M.</creator><creator>Braggio, Esteban</creator><creator>Hanson, Curtis A.</creator><creator>Shanafelt, Tait</creator><general>Elsevier Inc</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20211123</creationdate><title>Prevalence and Overall Survival of Low Count Monoclonal B-Cell Lymphocytosis (LC-MBL): A Screening Study of 8,297 Individuals from the Mayo Clinic Biobank</title><author>Slager, Susan L. ; Parikh, Sameer A. ; Achenbach, Sara J. ; Kleinstern, Geffen ; Boddicker, Nicholas J. ; Norman, Aaron D. ; Rabe, Kari G. ; Lesnick, Connie E. ; Call, Timothy G. ; Olson, Janet E. ; Cerhan, James R. ; Kay, Neil E. ; Vachon, Celine M. ; Braggio, Esteban ; Hanson, Curtis A. ; Shanafelt, Tait</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1850-d4be441966bc6cb307d9255dc56596817595047c05c3db1bcbd49c80e9f37a003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Slager, Susan L.</creatorcontrib><creatorcontrib>Parikh, Sameer A.</creatorcontrib><creatorcontrib>Achenbach, Sara J.</creatorcontrib><creatorcontrib>Kleinstern, Geffen</creatorcontrib><creatorcontrib>Boddicker, Nicholas J.</creatorcontrib><creatorcontrib>Norman, Aaron D.</creatorcontrib><creatorcontrib>Rabe, Kari G.</creatorcontrib><creatorcontrib>Lesnick, Connie E.</creatorcontrib><creatorcontrib>Call, Timothy G.</creatorcontrib><creatorcontrib>Olson, Janet E.</creatorcontrib><creatorcontrib>Cerhan, James R.</creatorcontrib><creatorcontrib>Kay, Neil E.</creatorcontrib><creatorcontrib>Vachon, Celine M.</creatorcontrib><creatorcontrib>Braggio, Esteban</creatorcontrib><creatorcontrib>Hanson, Curtis A.</creatorcontrib><creatorcontrib>Shanafelt, Tait</creatorcontrib><collection>CrossRef</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Slager, Susan L.</au><au>Parikh, Sameer A.</au><au>Achenbach, Sara J.</au><au>Kleinstern, Geffen</au><au>Boddicker, Nicholas J.</au><au>Norman, Aaron D.</au><au>Rabe, Kari G.</au><au>Lesnick, Connie E.</au><au>Call, Timothy G.</au><au>Olson, Janet E.</au><au>Cerhan, James R.</au><au>Kay, Neil E.</au><au>Vachon, Celine M.</au><au>Braggio, Esteban</au><au>Hanson, Curtis A.</au><au>Shanafelt, Tait</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prevalence and Overall Survival of Low Count Monoclonal B-Cell Lymphocytosis (LC-MBL): A Screening Study of 8,297 Individuals from the Mayo Clinic Biobank</atitle><jtitle>Blood</jtitle><date>2021-11-23</date><risdate>2021</risdate><volume>138</volume><issue>Supplement 1</issue><spage>2632</spage><epage>2632</epage><pages>2632-2632</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract><![CDATA[Monoclonal B-cell lymphocytosis (MBL) is one of the most common pre-malignant conditions and is characterized by a circulating population of clonal B-cells with an absolute clonal B-cell count < 5x10 9/L and no evidence of lymphadenopathy, organomegaly, or cytopenias. MBL can be classified by the immunophenotype: CLL-like MBL (CD5+, CD20dim), atypical MBL (CD5+, CD20+), or non-CLL-like MBL (CD5-, CD20+), as well as by the size of the clone (low-count or high-count) with low-count MBL (LC-MBL) defined as clonal B-cell <0.5x10 9/L or percent clonal B-cell count <85% out of total B-cell count. The prevalence of MBL varies depending on detection methods and population tested. In a Spanish screening study of 608 individuals, they identified 73 MBLs (12%) with CLL-like MBL; moreover, these authors also evaluated overall survival (OS) compared to 290 individuals without MBL and found a significantly shorter OS among these predominantly LC-MBLs. Here, we evaluate the prevalence and OS of LC-MBL in a large screening cohort of 8,297 individuals.
Study participants from the Mayo Clinic Biobank, a large-scale biorepository of adult patients, who had no prior history of hematologic malignancy, provided blood samples between 7/2009 to 4/2021. Stored peripheral blood mononuclear cells were screened for MBL with an eight-color flow cytometry assay capable of detecting clonal B-cell event to the 0.005% level. We classified each MBL by immunophenotype as CLL-like MBL, atypical MBL, and non-CLL-like MBL. Individuals with more than one immunophenotype were classified into one immunophenotype based on the following hierarchy: CLL-like MBL, then atypical MBL, then non-CLL like MBL. Based on previously published evidence, individuals were also classified by clonal counts using the percent clonal B-cell count <85% out of the total B-cell count to define LC-MBL. Individuals were followed from sample date to the earliest of death, loss to follow-up, or 5/31/2021. OS for LC-MBL and controls (individuals who screened negative for MBL) was assessed by Kaplan-Meier method. Age- and sex-adjusted OS was analyzed using inverse weights methods. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs), adjusted for age and sex.
We screened 8,297 individuals 40 years or older (median age 67 years, 39% male) and identified 1,326 (16%) with LC-MBL and 6,651 (80%) controls. Those individuals detected with high-count MBL (N=90, 1%) or individuals who had insufficient cells for flow cytometry interpretation (N=230, 3%) were excluded from subsequent analyses. The prevalence of LC-MBL was higher in males (21%) than females (14%; p<0.01) and significantly increased with age (p<0.01) ranging from 3% among those 40-49 years, 10% among those 50-59 years, 15% among those 60-69 years, 23% among those 70-79 years, and 29% for those 80+ years. Sixty-one individuals had clones with more than one type of immunophenotype. Based on our hierarchy, CLL-like MBL was the most common (N=1,155), followed by non-CLL-like (N=168) and atypical MBL (N=67). The median follow-up time in our cohort was 26 months (range 0-142), and 432 individuals had subsequently died. The 5-year and 10-year OS adjusted for age and sex among LC-MBLs was 95% and 87%, respectively; control estimates were 95% and 84%, respectively. We did not observe a significant difference in OS between those individuals with LC-MBL versus controls (HR=0.98, CI=0.77-1.24, P=0.84, Fig 1a), nor when we stratified individuals by age <65 (P=0.77) or age >= 65 (P=0.68). Among females, OS was longer among LC-MBL compared to controls (HR=0.61, CI=0.38-0.97, P=0.04); but no evidence of a difference in OS among males was observed (HR=1.22, CI=0.92-1.62, P=0.17). When we evaluated OS by MBL immunophenotype, we observed no statistically significant difference (Fig 1b, log rank P=0.44). When we stratified the MBLs by immunophenotype versus controls, we also did not observe a difference: CLL-like (HR=0.91, CI=0.71-1.18, P=0.5), atypical (HR=1.73, CI=0.92-3.27, P=0.09), non-CLL like (HR=0.98, CI=0.58-1.66, P=0.95).
In the largest MBL screening cohort to date, LC-MBL was a common condition among adults 40 years or older reaching a prevalence as high as 29% among individuals 80 years of age or older. OS among those with and without LC-MBL was similar, regardless of immunophenotype and age. The longer survival in females with MBL versus controls requires further evaluation.
[Display omitted]
Parikh: Pharmacyclics, AstraZeneca, Genentech, Gilead, GlaxoSmithKline, Verastem Oncology, and AbbVie: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics, MorphoSys, Janssen, AstraZeneca, TG Therapeutics, Bristol Myers Squibb, Merck, AbbVie, and Ascentage Pharma: Research Funding. Kay: Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding; Targeted Oncology: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Research Funding; Sunesis: Research Funding; Dava Oncology: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Behring: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Research Funding; MEI Pharma: Research Funding; Tolero Pharmaceuticals: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; CytomX Therapeutics: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios Pharm: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees. Shanafelt: Genentech, Pharmacyclics: Research Funding.]]></abstract><pub>Elsevier Inc</pub><doi>10.1182/blood-2021-153320</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-4971 |
| ispartof | Blood, 2021-11, Vol.138 (Supplement 1), p.2632-2632 |
| issn | 0006-4971 1528-0020 |
| language | eng |
| recordid | cdi_crossref_primary_10_1182_blood_2021_153320 |
| source | EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| title | Prevalence and Overall Survival of Low Count Monoclonal B-Cell Lymphocytosis (LC-MBL): A Screening Study of 8,297 Individuals from the Mayo Clinic Biobank |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T18%3A55%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Prevalence%20and%20Overall%20Survival%20of%20Low%20Count%20Monoclonal%20B-Cell%20Lymphocytosis%20(LC-MBL):%20A%20Screening%20Study%20of%208,297%20Individuals%20from%20the%20Mayo%20Clinic%20Biobank&rft.jtitle=Blood&rft.au=Slager,%20Susan%20L.&rft.date=2021-11-23&rft.volume=138&rft.issue=Supplement%201&rft.spage=2632&rft.epage=2632&rft.pages=2632-2632&rft.issn=0006-4971&rft.eissn=1528-0020&rft_id=info:doi/10.1182/blood-2021-153320&rft_dat=%3Celsevier_cross%3ES0006497121045778%3C/elsevier_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rft_els_id=S0006497121045778&rfr_iscdi=true |